Approximately 350 million people are chronically infected by the hepatitis B virus (HBV) worldwide, and an increasing percentage of these patients present themselves with HBeAg-negative disease. In many parts of the world, such as Southern and Central europe or also Iran, HBeAg-negative hepatitis B nowadays accounts for the majority of cases. HBeAg-negative hepatitis B develops spontaneously during chronic infection through mutations in the precore or core promoter region of the HBV genome, either ablating HBeAg expression by a stop codon in the precore region (called 'precore' [PC] mutation) or suppressing transcription of the precore RnA by a basal core promoter variation (termed ‘basal core promoter’[BCP] mutation).